Small Molecule Carboxylates Inhibit Metallo-β-lactamases and Resensitize Carbapenem-Resistant Bacteria to Meropenem.

ABSTRACT: In the search for new inhibitors of bacterial metallo-β-lactamases (MBLs), a series of commonly used small molecule carboxylic acid derivatives were evaluated for their ability to inhibit New Delhi metallo-β-lactamase (NDM)-, Verona integron-encoded metallo-β-lactamase (VIM)-, and imipenemase (IMP)-type enzymes. Nitrilotriacetic acid (3) and N-(phosphonomethyl)iminodiacetic acid (5) showed promising activity especially against NDM-1 and VIM-2 with IC₅₀ values in the low-to-sub μM range. Binding assays using isothermal titration calorimetry reveal that 3 and 5 bind zinc with high affinity with dissociation constant (K_d) values of 121 and 56 nM, respectively. The in vitro biological activity of 3 and 5 again

SUBMITTER: Tehrani KHME 

PROVIDER: S-EPMC7296533 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature